NZ331615A

NZ331615A - Components comprising a polymeric material blended with carbon black for inhalation devices

Info

Publication number: NZ331615A
Application number: NZ331615A
Authority: NZ
Inventors: Carin Widerstrom
Original assignee: Astra Ab
Priority date: 1996-03-22
Filing date: 1997-03-20
Publication date: 2000-02-28
Also published as: MY132493A; IS4842A; TR199801869T2; AU709989B2; SK129298A3; NO984313L; SE9601126D0; KR20000064736A; PL328950A1; WO1997034653A1; CZ300798A3; ID16289A; CA2248050A1; AR006359A1; EP0910422A1; BR9708135A; CN1213975A; AU2186697A; JP2000507132A; IL126069A0

Abstract

A component for use in an inhalation apparatus is described. The component is made of or is coated with a polymeric material loaded with carbon black in an amount sufficient to impart to the polymeric material a specific volume resistivity of less than 109 Ohmcm.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number 331 615 pi548-iwo [r-; PCT/ SE 9 7 / 0 0 4 7 0 " ! 0 3 -06- 1998 i . " -c < i— I) COMPONENTS FOR INHALATION DEVICES The present invention relates to components for inhalation devices for inhaling medicament, especially those components which can affect airborne particles or come into 5 contact with medicament Inhalation devices include dry powder inhalers, intended to dispense medicament which is m the form of a dry powder, and pressurised metered dose inhalers, which generally contain a medicament dissolved or suspended in a liquefied propellant gas, optionally 10 together with surfactants and other excipients The mechanism for dispensing the medicament varies between inhalers, but in general the medicament must exit the body of the inhaler and pass through a channel to a mouthpiece The mouthpiece may connect with a spacer, tnat is a dispersion chamber designed to facilitate inhalation 15 Pressurised metered dose inhalers release a metered dose of medicament upon each actuation, and for maximum benefit wi'h direct inhalation a degree of co-ordination between actuation and inhalation is required Powder inhalers are actuated by the air flow generated at inhalation and for maximum benefit a certain air flow is required With a spacer, the medicament is dispensed into the spacer chamber from where it can be inhaled 20 simply by breathing normally The residence time of the medicament in the spacer can be from a few seconds to several minutes, for example An example of a dry powder inhaler is the Turbuhaler® inhaler Examples of spacers include the Nebuhaler® and Nebuchamber® spacers 25 In the course of inhalation, medicament will come into contact with various parts of an inhalation device, including for example the body, channel and mouthpiece of an inhaler, and a spacer Such components are generally (but not essentially) made of a polymeric material, for example, a polypropylene or a polyethylene, which is moulded into the 30 required shape AMBfDFD SHEET Di548-lWO PCT/SE97 / 0 0 4 7 0 0 3 -06- 1998 Not all of a nominal dose of medicament from an inhaler will reach its intended target, which may be, for example, the lungs The medicament which does not reach the target is lost, for example, m the inhaler, mouth and respiratory tract Clearly, the amount of 5 wastage should be as low as possible WO-A-91/19524 describes an inhaler for inhaling pulverulent medicament from within a capsule, including a capsule chamber which may be formed of components made of a polymeric material with low surface resistivity in order to minimise the extent to which io released powdered medicament can agglomerate on the surface of the a:r passage through the inhaler The surface resistivity desired is preferabl} less than 10i: Ohms and more preferably less than 108 Ohms The polymeric material may incorporate carbon or steel fillei, for example, in the form of fibres or non-fibrous chemical additives As examples of the polymeric material are mentioned a polyether block amide product with chemical 15 additives and a range of polypropylenes with chemical additives The inhaler also includes a modthpiece, which may be integral with the chamber, preferably having at least its inner wall formed from such a polymeric material of low surface resistivity WO-A-95/20414 describes a spacer for children, primarily intended to bejused in :o conjunction with a pressurised metered dose inhaler The spacer is made from stainless steel, which has a surface resistivity such that electrostatic attraction between the respirable particles and spacer walls is minimised The ^I'jface resistivity is less than 10? Ohm, preferably less than 10^ Ohm and most preferably less than 1 Ohm 25 The present invention is concerned with polymeric materials in components for inhalation devices It has been found that the amount of medicament which is retained in a device composing components made of a polymeric maternal can be significantly reduced by incorporating carbon black into the polymeric material Components according to the present invention have anti-static properties which minimise the amount of medicament 30 retained on component surfaces AMB'DE) SHEET PCT / St 9 7 / 0U4 / u D1548-IWO r~. i- Z'~J 0 3 -06- 1998 3 Carbon blacks are obtainable, for example, from Degussa AG, Frankfurt, Germany They are chemically and physically well-defined products, which are manufactured by incomplete combustion of oils or gases, and are composed of more than 96 percent by 5 weight of finely dispersed carbon with small amounts of oxygen, hydrogen, nitrogen and sulohur They may be produced for example, as dispersions, pastes, chips or pellets Today, the most important method for the manufacture of carbon blacks is the so-called "furnace black" process This process can produce a large variety of carbon blacks, for example, with particular particle sizes and specific surface areas It >Wo permits the L V io control of particle aggregation, that is, the carbon black struciure Carbon blacks consist of chained-branched aggregates of approximately spherical primary" particles Extensive branching or interlinking produces carbon black having a 'high structure", while less extensive interlinking produces a "low structure ' carbon black One method for the dp termination of structure is the "DBP absorption" test, which is described in ISO 4656 15 and ASTM D-2414 In this method, dibutylphthalate (DBP) is added dropwise to a certain amount of carbon black that has been placed in a calibrated kneading machine and the torque exerted by the kneading machine is measured A change in the torque indicates that all of the voids between the carbon black aggregates have been filled with DBP and the surface has been wetted The consumption of DBP thus allows determination of the degree 20 of aggregation of the carbon black In general, the higher the DBP absorption in ml /100 g (the "DBP number"), the higher the carbon black structure Carbon blacks with a low structure have a DBP number o? less than 70 ml/100 g of carbon black, those with a medium structure have a DBP number of between 70 and 100 ml/100 g of carbon black, and those with a high structure have a DBP number of above 110 ml/i00 g of carbon black 25 So-called "extra-conductive" carbon blacks typically have a DBP number in excess of,300 ml/100 g of carbon black The primary use of carbon blacks is in the reinforcement of rubber, for pigmentation, UV stabilisation and as conductive blacks 30 AMENDED SHEET d 1548-1wo ^PCT/ SE 9 7 / 0 0 4 7 0 0 3 -06- 1998 t 4 J Accordingly, the present invention provides a component for use m an inhalation device, said component being made of or coated with a polymenc matenal loaded with carbon black having a DBP number of more than 300 ml/100 g of carbon black and m an amount of between 3 and 15 percent by weight of the polymenc matenal to impart to the polymenc 5 matenal a spec/iie volume resistivity of less than 109 Ohmcm The present invention also extends to an inhalation device, in particular a spacer, incorporating the component as descnbed above Preferably, the specific volume resistivity of the polymeric matenal is less than about 1Cf Ohmcm more preferably less than about 10* Ohmcm In an especially preferred embodiment the specific volume resistivity of the polymenc material is less than about 102 Ohmcm is Specific volume resistivity may be measured using commercially available apparatuses for measuring conductivity > ;The use of a carbon black dispersion is particularly advantageous as good dispersion of the carbon black in the polymeric material can be achieved Preferably, the carbon black-20 loaded polymenc matenal compnses a homogeneous distnbution of the carbon black ;The very low specific volume resistivity values which may be achieved in accordance with the present invention are particularly valuable when the component is incorporated in a spacer In a spacer, a comparatively long medicament residence time is necessary, and the 25 longer the residence time, the more opportunity there is for the medicament to "attach" to the spacer walls ;It will be understood that the component of the present invention may be other than that incorporated in a spacer For example, the component may compose the body, a channel, 30 or the mouthpiece of an inhaler amended sheet ;D1548-IWO F j PCT/ SE9 7 / 00 4 70 ;f~ "C vcn 0 3 -06- 1998 ;t ;Preferably, carbon black is included m an amount of between 6 and 10 percent and especially between 8 and 10 percent by weight of the carbon black-loaded polymenc matenal ;5 ;More preferably, carbon black is included in an amount of around 10 percent, or around 9 percent or around 8 percent, or around 7 peicent, or around 6 percent, or around 5 percent, or around 4 percent by weight of the carbon black-loaded polymeric matenal io Suitable carbon blacks are commercially available, for example from Degussa AG, or from Cabot Plastics, Belgium Examples of Degussa AG carbon blacks are the range of carbon blacks known as Pnntex®, for example "Pnntex L", "Pnntex L 6", and the extra-conductive "Printex XE 2" ;15 The polymeric matenal can be any which can be moulded into the desired shape For example, the polymenc matenal may be a polypropylene, a polyethylene, a polyester, a polycarbonate, a polystyrene, a polyoxyethylene, a fluoropolymer, or a copolymer thereof Suitable polymeric materials may be obtained, for example, from Hoechst AG, Frankfurt, Germany As specific examples of polymenc materials may be mentioned the ;20 polyethylenes Hostalen® and Hostalen GUR®, the polypropylenes Hostalen PP® and Hostacen®, as well as Topas®, Hostaform®, Kemetal®, Celanex®, Vandar®, Impet®, Celstram®, Fortron®, V-ctra® and Hostaflon®, all available from Hoechst AG Preferably, the polymeric matenal is a polypropylene or a polyethylene ;25 The carbon black-loaded polymenc matenal, and the homogeneous mixture, may be manufactured by conventional methods, for example, by extrusion of the polymenc matenal together with the carbon black The mixing parameters, flow conditions and cooling conditions may be optimised easily by methods well known to a person skilled in the art, according to the particular polymeric material and carbon black used ;30 ;AMENDED SHEET ;0 3 -05-1998 ;« » ;6 ;Carbon black-loaded polymenc matenals are also commercially available, for example, from Premix Oy, Rajamaki, Finland ;The components according to the present invention may be made by conventional moulding techniques, for example, by injection moulding or by blow moulding The moulding parameters may be optimised easily by a person skilled m the art, according to the particular matenals used The preferred method of manufacture is injection moulding Typical injection moulding parameters may be for example a cylinder nozzle temperature of from 200 to 250 °C, a mould temperature of from 30 to 80 °C an injection pressure of from 600 to 1800 bar and a moderate injection speed Preferably, a low moulding speed is used initially and slowly increased dunng the moulding process Preferably, the back pressure is as low as technically possible Preferably, the ma'enal for injection moulding is pre-dned for example, at from 75 to 80 °C for up to 4 hours, typically from 2 to 4 hours ;The present invention a'so orovides a method of forming the component for use in an inhalation device as de icnbed above, compnsing the step of moulding the component at least in pan from a carbor black-loaded polymenc material ;When the carbon black-loaded polymeric matenal is a coating on another.polymenc matenal, it may be co-moulded with the other polymenc matenal, for example, using two extruders, to produce a moulded component in which the carbon black-loaded polymeric material is surrounded by the other matenal, that is, the "inner" surface of the component is of the carbon black-loaded polymenc matenal and the "outer" surface of the component is of the other polymenc matenal The outer matenal may be provided with any desired pigmentation to mask the black colour of the carbon black in circumstances where this would be considered undesirable ;The thickness of the component or carbon black-loaded polymenc layei may vary according to the nature of the moulded component Where the component is incorporated ;SHEET ;$ ;D1548-1 WO y- , ' - TP ~ ;20 ;25 ;k ;- :z: ?n ;PCT/ SE97 / 0 0 4 70 0 3 -05-1998 ;7 ;m a spacer, for example, the thickness of the carbon black-loaded polymenc matenal may be, for example, up to about 10 mm, preferably between 1 and 5 mm thick ;The present invention will be further described with reference to the following non-limiting 5 Examples ;Example 1 ;A carbon black-loaded polymenc material, "PP 1381" (formerly "Pre-Elec TP 4474"), io Pramix Oy, composing polypropylene '"Hostalen PPU 1734S1", Hoechst AG and 9 ;percent by weight of "Pnntex XE 2" carbon black Degussa AG, was used to manufacture a spacer for use with a dry powder inhaler, by injection moulding using a "Ferromatic" ;injecuon moulder, with a cylinder nozzle temperature of 240 °C, a mouid cavity ;# ;temperature of 30 °C, an injection pressure of 1700 bar, a back pressure of 1600 bar and a is moderate injection speed ;The specific volume resistivity obtained was 100 Ohmcm (Surface resistivity 1300 Ohm ) ;Example 2 ;A carbon black-loaded polymenc material, "Pre-Elec TP 4479", Premix Oy, compnsing polypropylene "Hostalen PPU 1734S1", Hoechst AG, and 22 percent by weight "Black Pearls 4750" carbon black, Cabot Plastics, was used to manufacture a spacer for use with a dry powder inhaler, by injection moulding as in Example 1 ;The specific volume resistivity obtained was 30 Ohmcm (Surface resistivity 800 Ohm ) Example 3 ;AMENDED SHEET ;—i PCT/SE97 / 0 0 4 70 ;] ;— =-* 0 3 -06- 1998 i 8 A carbon black-loaded polymenc matenal, "Pre-Elec TP 4480", Premix Oy, compnsing polypropylene "Hostalen PPU 1734S1", Hoechst AG, and 37 percent by weight "Channel Black MPC" carbon black, Cabot Plastics, was used to manufacture a spacer for use with a dry powder inhaler, by injection moulding as in Example 1 The specific volume resistivity obtained was 10000 Ohmcm (Surface resistivity 100000 Ohm) Example 4 Doses of budesonide from a dry powder inhaler (Pulmicort Turbuhaler®) containing 200 unit doses each comprising 400 jig of budesonide were expelled by means of a suction flow into a spacer according to Example 1 above After a 2 second delay suction flow means were employed to expel the dose from the spacer onto a filter i 11 The experiment was repeated using a spacer constructed of polypropylene only The means of manufacture of the polypropylene-only spacer was as in Example 1. but with an injection pressure of 900 bar and a back pressure of 600 bar The amount of budesonide on the filter after expulsion from the carbon black-loaded polypropylene spacer of Example 1 was 2 4 times greater than the amount resulting from expulsion from the conventional polypropylene spacer. This was taken as an indication of the greatly reduced amount of medicament which had been retained in the spacer according to the present invention as compared with a conventional spacer Example 5 Doses of budesonide from a dry powder inhaler (Pulmicort Turbuhaler®) containing 200 unit doses each comprising 400 |i,g of budesonide were expelled by means of a suction flow AMTOED SHEET </div>

Claims

<div class="application article clearfix printTableText" id="claims">



r 

D154S-1WO 

PCT/SE9 7 / 0 0470 

0 3 -06- 1998 

9 

into a spacer according to Example 1 above After a 30 second delay, suction flow means were employed to expel the dose from the spacer onto a filter 

The experiment was repeated using a spacer constructed of polypropylene only The means 5 of manufacture of the polypropylene-only spacer was as m Example 1, but with an mjectron pressure of 900 bar and a back pressure of 600 bar 

The amount of budesonide on the filter after expulsion from the carbon black-loaded polypropylene spacer of Example 1 was 2 8 times greater than the amount resulting from io expulsion from the conventional polypropylene spacer This was taken as an indication of the greatly reduced amount of medicament which had been retained in the spacer according to the present invention as compared with a conventional spacer 

9 

MH01O® SrtE£t 

10 

CLAIMS 

1 A component for use m an inhalation device, said component being made of or coated with a polymenc matenal loaded with carbon black having a DBP number of more than 300 ml/100 g of carbon black and m an amount of between 3 and 15 percent by weignt of the polymenc matenal to impart to the polymenc matenal a specific volume resistivity of less than 109 Ohmcm
2 The component of claim 1, wherein the specific volume resistivity is less than 106 Ohmcm
3 The component of claim 2, wherein the specific volume resistivity is less than 102 Ohmcm 

*
4 The component of any of claims 1 to 3, wherein the carbon black is a carbon black dispersion
5. The component of any of claims 1 to 4, wherein the carbon black-loaded polymeric matenal comprises a homogeneous mixture of carbon black and polymenc material
6 The component of any of claims 1 to 5, wherein the carbon black-loaded polymeric matenal compnses carbon black m an amount of between 8 and 10 percent by weight of the polymenc matenal
7 The component of any of claims 1 to 6, wherein the polymenc matenal is a polypropylene, a polyethylene, a polyester, a polycarbonate, a polystyrene, or a copolymer thereof
8 The component of any of claims 1 to 6, wherein the polymenc material is a polypropylene or a polyethylene 

AMENDED SHEET 

^ D1548-1WO 

PCT/SE9 7 /-0-C4 7 0 0 3 -06- 1998 

11 

$
9 The component of any of claims 1 to 8, wherein the component is one of the body of an inhaler, the mouthpiece of an inhaler or a channel of an inhaler 

5
10 An inhalation device incorporating the component of any of claims 1 to 8
11 A spacer incorporating the component of any of claims 1 to 8
12 A method of forming the component of any of claims 1 to 8, comprising the step of to moulding the component at least in part from a carbon black-loaded polymenc matenal
13. A component according to claim 1 substantially as herein described or exemplified.
14. An inhalation device according to claim 10 substantially as herein described or exemplified.
15. A spacer according to claim 11 substantially as herein described or exemplified.
16. A method according to claim 12 substantially as herein or exemplified, 

ioi-.t i ' \ 

| 17 J'V-5 I 

\ RPCEWcD. : 

AMENDED SHEET 



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